A rapid and simplified method for the isolation of the rat intestinal vitamin D-dependent CaBP developed and the dissociation constant (0.5 micromoles) and maximum binding capacity (0.24 umol of Ca2 ion/mg protein) established for a highly purified preparation. Changes in the purified CaBP were shown to parallel the experimental decay growth rate in animals and state of nutrition utilizing antibody detection analyses. It was also established that the rat placenta contains a CaBP which is immunologically identical to the intestinal CaBP and that this placental CaBP is essential for maternal-fetal calcium exchange in the rat and mineralization of the fetal skeleton. Studies in humans with chronic uremia and filtration rates less than 5 ml/min demonstrated that the intestinal CaBP is normal in activity, quantity and affinity for Ca 2 ion. Human intestinal CaBP activity correlated directly with circulating 250 HD3 levels but were unrelated to circulating parathyroid hormone values. It was also demonstrated that lithium (Li) therapy in growing experimental animals (with blood Li values approximately those of humans on this medication) resulted in significant suppression of bone formation and mineralization rates and hypercalciuria with no change in circulating parathyroid hormone. Li was also shown to affect the renal biological response to parathyroid hormone with alterations in the cAMP and phosphaturic response documented.